The overall goal of this Program Project is to identify trait alleles that contribute to variation in human fear and anxiety. Project 3 will provide a large community based human sample evaluated for cued fear conditioning and two heritable, clinically relevant dimensional anxiety measures (NEO Personality Inventory, Anxiety Sensitivity Index). Individuals will also provide a blood sample for DNA. The combined work of the neurobiology (Drs. Kandel and Hen, Projects 1A, 1B) and molecular genetics (Dr. Gilliam, Project 2) components of the program project will identify human candidate genes derived from knowledge of the molecular biology and neurocircuitry of fear conditioning and selected aspects of innate fear in animal models. These candidates will be scanned for allelic variance in the entire Project 3 sample to search for trait alleles for fear conditioning, the two dimensional assessments (NEO, ASI) and composite phenotypes derived from these measures. Data will be analyzed using both methods that regress continuous phenotypes to allelic variance across the whole sample and by comparison of phenotypic extremes. Trait alleles identified for any of these phenotypes will be evaluated as susceptibility loci for human anxiety disorders (Project 4, Dr. Weissman). The dimensional measures (NEO, ASI) will also be used as a "bridge" to further refine the selection of candidates and target sub-populations in the anxiety disorder subjects. As described in Project 2, the combined data from Projects 2, 3, 4 will be used to begin to explore multivariate models of anxiety that encompass the several phenotypes assessed in this grant.